2-(2',3'-Dihydrobenzofuran-4'-yl)cyclopropane carboxylate derivatives have been prepared via cyclopropylation of 3-(2',3'-dihydrobenzofuran-4'-yl)propenoic esters or amides using hazardous reagents such as diazomethane (Catt, J. D.; Johnson, G.; Keavy, D. J.; Mattson, R. J.: Parker, M. F.; Takaki, K. S.; Yevich, J. P. WO 98/25606, Jun. 18, 1998).
A more convenient method for the preparation of simple 2-arylcyclopropane carboxylates involves the .alpha.-bromination of 3-simple aryl substituted cyclobutanone with bromine followed by ring contraction of the resulting .alpha.-bromocyclobutanone (Lantzsch, R.; Arlt, D.; Jautelat, M. U.S. Pat. No. 4,681,952, Jul. 21, 1987). However, reaction of 2,2-dimethyl-3-(2',3'-dihydrobenzofuran-4'-yl)cyclo-butanone with bromine followed by ring contraction under these reaction conditions does not give the desired product without undesirable side products. Fusing a dihydrofuran ring to the phenyl group not only activates the phenyl ring for electrophilic aromatic bromination, but also provides more reactive benzylic and etheral sites for bromination compared to the desired reaction at the .alpha.-position adjacent to the ketone group. In the present invention, as will be seen, an enolate is preformed before bromination to overcome all the above mentioned side reactions, providing the desired 2-(2',3'-dihydrobenzofuran-4'-yl)cyclopropane carboxylates in high yield without costly chromatographic separation of products.
Several methods have been disclosed previously for the preparation of 3-aryl cyclobutanones (Lantzsche, R.; Arlt, D.; Janutelat, M. U.S. Pat. No. 4,681,952, Jul. 21, 1987, and Falmagne, J.-B.; Escudero, J.; Taleb-Sahraoui, S.; Ghosez, L. Angew. Chem. Int. Ed. Engl., 1981, 20, 879), among which [2+2]-cycloaddition of styrene with a ketene precursor has its advantages (Falmagne, J.-B. et al, supra). While styrene itself has been successfully used in the [2+2]-cycloaddition under acidic conditions with elevated temperatures for the cycloaddition, it is not apparent if the dihydrofuran fused styrenes will survive under such acidic conditions with elevated temperatures. Dihydrofuran fused styrenes are expected to be more prone to acid catalyzed and heat induced polymerization than styrene.
Preparation of 3-phenylcyclobutanone with .alpha.-chloroenamine has also been reported (Houge, C.; Frisque-Hesbain, A. M.; Mockel, A.; Ghosez, L. J. Am. Chem. Soc., 1982, 104, 2920.